This project focuses on the interactions between experience and adult neurogenesis in the hippocampal region of the brain. We are interested in understanding how experiences, including learning and stressful experiences, regulate adult neurogenesis and how the new neurons alter responses in these situations. We study the regulation and function of adult neurogenesis in rats and mice, which show continued production of new neurons throughout adulthood similar to that in primates, including humans. We have previously found that specifically inhibiting adult neurogenesis in mice increases their hormonal and behavioral responses to stress, increasing depressive-like behavior. During the past year, we have focused on identifying structural and behavioral changes that occur when adult neurogenesis is inhibited using pharmacogenetic manipulations in mice or rats. To do this, we have recently developed a transgenic rat in which neurogenesis can be specifically inhibited using an antiviral drug. The availability of a rat model with specific ablation of new neurons enables us to study more complex tasks that are within the rat behavioral repertoire and also to take advantage of the larger brain size for structural studies. We have used these rats to investigate the effects of the rapidly-acting antidepressant ketamine on neurogenesis. We find that ketamine enhances the incorporation of new neurons into functional networks within hours, more quickly than any previously identified treatment. However, when we inhibited neurogenesis prior to giving ketamine, we found that the antidepressant-like effect of ketamine on eating in an unknown environment does not depend on adult-born neurons.